Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease.

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.

Circulating lipoprotein profiles are modulated differently by lipoprotein lipase in obese humans.

BACKGROUND: Several genetic analyses have suggested that lipoprotein lipase (LpL) genotypes causing decreased LpL activity correlate with increased triglyceride concentrations and risk for coronary artery disease. In contrast, in some other studies LpL activity was positively correlated with plasma low-density lipoprotein (LDL) cholesterol concentrations. OBJECTIVE: To assess whether these different associations represent physiologic differences in lipoprotein metabolism. METHODS: We correlated postheparin lipase activities, postprandial lipemia, and fasting lipoprotein concentrations in obese (BMI > or = 30 kg/m2, n = 26) and non-obese (BMI < or = 30 kg/m2, n = 57) individuals. LpL was measured using specific inhibitory antibodies. RESULTS: Surprisingly, LpL activity was significantly correlated with triglyceride area under the curve after a fat load in the non-obese, but not the entire group. Moreover, in non-obese individuals, LpL activity correlated directly (r = 0.40) and hepatic lipase activity correlated inversely (r = -0.32) with high-density lipoprotein (HDL) cholesterol concentrations. These relationships were not found in the obese group, in whom LpL correlated with LDL cholesterol concentrations (r = 0.54). CONCLUSIONS: We conclude that postheparin LpL activity relates to different lipoproteins in obese and non-obese individuals. In obesity, greater LpL activity may enhance conversion of very-low-density lipoprotein cholesterol to LDL cholesterol, whereas in non-obese individuals the correlation is with HDL cholesterol. Whether this is due to differences in the source of LpL (muscle or fat), or to other associated alterations in lipoprotein metabolism is unknown. These results may explain the non-uniformity of correlations between LpL and atherogenic lipoproteins in different populations.

HDL-subpopulation patterns in response to reductions in dietary total and saturated fat intakes in healthy subjects.

BACKGROUND: Little information is available about HDL subpopulations during dietary changes. OBJECTIVE: The objective was to investigate the effect of reductions in total and saturated fat intakes on HDL subpopulations. DESIGN: Multiracial, young and elderly men and women (n = 103) participating in the double-blind, randomized DELTA (Dietary Effects on Lipoproteins and Thrombogenic Activities) Study consumed 3 different diets, each for 8 wk: an average American diet (AAD: 34.3% total fat,15.0% saturated fat), the American Heart Association Step I diet (28.6% total fat, 9.0% saturated fat), and a diet low in saturated fat (25.3% total fat, 6.1% saturated fat). RESULTS: HDL(2)-cholesterol concentrations, by differential precipitation, decreased (P < 0.001) in a stepwise fashion after the reduction of total and saturated fat: 0.58 +/- 0.21, 0.53 +/- 0.19, and 0.48 +/- 0.18 mmol/L with the AAD, Step I, and low-fat diets, respectively. HDL(3) cholesterol decreased (P < 0.01) less: 0.76 +/- 0.13, 0.73 +/- 0.12, and 0.72 +/- 0.11 mmol/L with the AAD, Step I, and low-fat diets, respectively. As measured by nondenaturing gradient gel electrophoresis, the larger-size HDL(2b) subpopulation decreased with the reduction in dietary fat, and a corresponding relative increase was seen for the smaller-sized HDL(3a, 3b), and (3c) subpopulations (P < 0.01). HDL(2)-cholesterol concentrations correlated negatively with serum triacylglycerol concentrations on all 3 diets: r = -0.46, -0.37, and -0.45 with the AAD, Step I, and low-fat diets, respectively (P < 0.0001). A similar negative correlation was seen for HDL(2b), whereas HDL(3a, 3b), and (3c) correlated positively with triacylglycerol concentrations. Diet-induced changes in serum triacylglycerol were negatively correlated with changes in HDL(2) and HDL(2b) cholesterol. CONCLUSIONS: A reduction in dietary total and saturated fat decreased both large (HDL(2) and HDL(2b)) and small, dense HDL subpopulations, although decreases in HDL(2) and HDL(2b) were most pronounced.

A common Hpa I RFLP of apolipoprotein C-I increases gene transcription and exhibits an ethnically distinct pattern of linkage disequilibrium with the alleles of apolipoprotein E.

Apolipoprotein (apo) C-I is a constituent of triglyceride-rich lipoproteins (TGRL) that interferes with their hepatic clearance. Functional polymorphism in the apoC-I gene has not been established. We determined that an Hpa I site variably present at -317 relative to the apoC-I gene is produced by a 4-bp CGTT insertion. The apoC-I Hpa I alleles showed an ethnically distinct pattern of linkage disequilibrium with the alleles of the adjacent apoE gene. The frequency of apoC-I Hpa I-positive (H2) with apoE varepsilon2 was 0. 98, without significant ethnic difference. In contrast, the frequency of H2 with apoE epsilon4 was 0.85 in European-Americans but only 0.55 in African-Americans (P < 0.001). The frequency of H2 with apoE epsilon3 was 0.02 in European-Americans and 0.08 in African-Americans (P < 0.001). African-American apoE epsilon3/epsilon3 carriers of apoC-I H2 had 19% lower fasting triglyceride levels than H1 homozygotes (P = 0.03) along with 18% higher HDL-cholesterol levels (P = 0.02). ApoB levels were 21% lower (P = 0.002). H2-allelic reporter-gene constructions showed 50% higher expression in transient transfection studies. We localized the source of this difference in expression to the CGTT insertion itself. Deletion studies of the H1 allele showed a negative transcriptional effect of the polymorphic region. An H1 oligodeoxynucleotide showed specific binding of a hepatoma-cell nuclear protein not evident with an H2 oligodeoxynucleotide. The H2 sequence may decrease the binding of a negatively acting transcription factor, leading to overexpression of apoC-I. This may produce a functional effect on lipoprotein levels but confirmation is needed in other populations.

LPL promoter -93T/G transition influences fasting and postprandial plasma triglycerides response in African-Americans and Hispanics.

The lipoprotein lipase (LPL) promoter -93T/G transition has previously been reported as having a triglyceride (Tg)-lowering effect, whereas the D9N variant has been shown to have a Tg-raising effect. These two variants were studied in 66 healthy subjects of Hispanic and 42 subjects of African-American origin, who had participated in a study of postprandial lipemia. While the allele frequency of the -93G was significantly different in the Hispanics and African Americans (0.09: 95% CI 0.04-0.13 and 0.28: 95% CI 0.19-0.38; P=0.0001, respectively), the N9 allele frequency was not different (0.06: 95% CI 0.02-0.1 and 0.05: 95% CI 0.002-0.093, respectively). Linkage disequilibrium between the -93T/G and D9N was highly significant in Hispanics (delta=0.67. P=0.0001), compared to delta=0.09 (NS) in African-Americans. In the combined group, compared to individuals with the common genotype (TT/DD; n=71) with fasting plasma Tg of 1.34 (+/-4.5% SEM) mmol/l, carriers of the G/D haplotype (TG/DD + GG/DD; n=25) had significantly lower plasma Tg levels of 1.08 (+/-10% SEM) mmol/l (P < 0.02). After the fat meal, compared to individuals with neither mutation, TT/DD, the effect of the G/D haplotype was to reduce significantly postprandial Tg (P < 0.036). Retinyl palmitate concentration at 5 hrs was significantly lower in G/D carriers than TT/DD individuals (P < 0.05). The lipid-raising effect of the N9 allele in carriers of the -93G (TG/DN + GG/DN) and effect on postprandial Tg clearance was not significant in this group. Thus carriers of the G/D haplotype have lower fasting plasma Tg and reduced alimentary lipemia. This allele may be associated with reduced risk of coronary artery disease.

Hormonal regulation of lipoprotein(a) levels: effects of estrogen replacement therapy on lipoprotein(a) and acute phase reactants in postmenopausal women.

Estrogen lowers lipoprotein(a) [Lp(a)] levels, but the mechanisms involved have not been clarified. To address the relationship between estrogenic effects on Lp(a) and serum lipids, and on other plasma proteins of hepatic origin, 15 healthy postmenopausal women participated in a randomized, double-blinded, placebo-controlled, crossover study with 4 weeks of oral conjugated estrogens (0.625 mg/d) and placebo, separated by a 6-week period. Lp(a) levels decreased during estrogen treatment in 14 of the 15 subjects (mean decrease, 23%; P < .001). In response to estrogen, apolipoprotein A-I (apoA-I), HDL cholesterol, and triglyceride levels increased by 12% (P = .001), 11% (P < .001), and 10% (P = .02), respectively. Apolipoprotein B (apoB) and LDL cholesterol levels decreased by 7% (P = .01) and 12% (P = .03), respectively, ApoB, LDL cholesterol, and Lp(a) levels fell within 1 week of treatment, whereas apoA-I and HDL cholesterol levels rose more slowly. Levels of acid alpha 1-glycoprotein (AAG) and haptoglobin (HPT), two hepatically derived acute phase proteins, also decreased during estrogen treatment by 18% (P < .001) and 25% (P = .002), respectively. Although the changes in AAG and HPT in response to estrogen were highly correlated (r = .67, P = .009), we were unable to detect a correlation between change in either acute phase protein and change in Lp(a) (r = -.14 and -.24, P = .64 and .41). The lack of correlation between the changes in two acute phase reactants and Lp(a) suggests different underlying mechanisms for the effects of estrogen on these liver-derived proteins.

Reactivity to smoking cues: mediating roles of nicotine dependence and duration of deprivation.

This study examined the roles of nicotine dependence and duration of smoking deprivation as mediators of smoking cue reactivity in 117 individuals enrolled in treatment. Participants were randomly assigned to 15, 90, or 180 min of deprivation; all were exposed to smoking cues (observing a research assistant smoke a cigarette) while a variety of self-report, behavioral, and psychophysiological measurements were obtained. Results indicated that in general, psychophysiological reactivity to smoking-relevant cues was greater with increasing deprivation; heart rate analysis revealed an interaction between nicotine dependence and duration of deprivation. Smoking desire, negative affect, physical withdrawal symptoms, and other ratings were interrelated during cue exposure, and generally demonstrated predicted relationships with the independent variables. Multiple regression analysis revealed that desire to smoke during cue exposure was predicted by a combination of psychophysiological, self-report, and demographic variables. These findings have implications for methodological considerations and theoretical underpinnings of smoking cue reactivity research.

Aggressiveness, dominance, developmental factors, and serum cholesterol level in college males.

The present study was conducted to examine for college males relations between aggressiveness (or expressive hostility) and dominance and (a) particular developmental experiences and (b) total serum cholesterol. Aggressiveness but not dominance was found to be positively related to subjects' reports of their parents' behavior which reflected (a) less genuine acceptance, (b) more interference in the person's desires as a child, and (c) more punitiveness. For low-physically fit subjects, both aggressiveness and dominance were found to be positively related to levels of total serum cholesterol. These relations are congruent with the notion that both aggressiveness and dominance may contribute to hastening coronary atherosclerosis and risk of CHD via elevated levels of plasma lipids. It should be noted, however, that the relations obtained in the present study were all modest in size. For high-physically fit individuals associations were not found between total serum cholesterol and either aggressiveness or dominance. These results suggest that good physical fitness may attenuate the degree to which either aggressiveness or dominance may adversely affect health via elevated levels of cholesterol.

Perceiving implied harmony: the influence of melodic and harmonic context.

Two experiments investigated the influence of melodic and harmonic context on the obviousness of pitch changes in 3 Western tonal melodies. In Experiment 1, listeners with different levels of musical skill heard standard melodies followed by comparison melodies in which single pitch changes could occur. In-key pitch changes that were not implied by the local harmony were judged more obvious than in-key pitch changes that were so implied. This effect was influenced by the surrounding context of melodic line and chords and was absent when the context contained chords that were not consistent with the harmony implied by the melodic line. In Experiment 2, with similar listeners, implied harmony effects were eliminated by removing parts of the melodic line, indicating the relative importance of melodic context as a determinant of implied harmony. Questionnaire data suggested that knowledge of tonal relationships was tacit, even in many trained listeners.

Increases in dietary cholesterol are associated with modest increases in both LDL and HDL cholesterol in healthy young women.

We studied the effects of dietary cholesterol intake on lipid and lipoprotein levels in healthy young women (n = 13) who were otherwise eating an American Heart Association (AHA) diet. The study used a randomized, three-way crossover design to determine the effects of 0, 1, or 3 eggs added per day (dietary cholesterol range, 108 to 667 mg/d). Each of the three diets was eaten for 8 weeks, with a washout period between diets. Three fasting blood samples were obtained during the last 3 weeks of each diet period to observe changes in fasting plasma lipid levels associated with the menstrual cycle. We also obtained blood just before and 4 and 8 hours after the subjects ingested a standard high-fat formula. During the menstrual cycle, total cholesterol and LDL cholesterol levels fell by 0.051 mmol/L (1.99 mg/dL) and 0.064 mmol/L (2.48 mg/dL) per week, respectively. HDL cholesterol concentrations increased by 0.060 mmol/L (2.3 mg/dL) per week during the first half of the cycle and then fell by 0.050 mmol/L (1.94 mg/dL) per week during the second half. Therefore, all statistical analyses were performed on values adjusted to midcycle. Total fasting cholesterol concentrations increased by 0.073 mmol/L (2.81 mg/dL) per 100 mg dietary cholesterol added to the diet per day (P = .001). LDL cholesterol increased by 0.054 mmol/L (2.08 mg/dL) per 100 mg/d dietary cholesterol (P = .003); this accounted for about 75% of the rise in total cholesterol. HDL cholesterol concentrations increased by 0.015 mmol/L (0.57 mg/dL) per 100 mg/d dietary cholesterol (P < .04). There was a wide range of responses among the women. Plasma apoB levels increased significantly, 0.93 mg/dL per 100 mg/d dietary cholesterol (P = .025), whereas apoA-I levels tended to rise (1.35 mg/dL per 100 mg/d, P = .056). Increases in dietary cholesterol did not produce any observable effects on fasting plasma cholesteryl ester transfer protein levels and had no effect on the response to a standard high-fat formula. Although menstrual-cycle changes in plasma total, LDL, and HDL cholesterol levels were observed, the effects of the diets were similar in the follicular and luteal phases of the menstrual cycle. Additionally, despite changes associated with the menstrual cycle, within-subject variation in plasma total cholesterol was actually smaller in this study than in our study of young men.

Sensitivity to event timing in regular and irregular sequences: influences of musical skill.

In two experiments, the performance of listeners with different amounts of musical training (high skill, low skill) was examined in a two-alternative forced choice time-detection task involving simple five-cycle acoustic sequences. In each of a series of trials, all listeners determined which of two pattern cycles contained a small time change. Sequence context was also varied (regular vs. irregular timing). In Experiment 1, in which context was manipulated as a between-subjects variable, high-skill listeners performed significantly better than low-skill listeners only with regular patterns. In Experiment 2, in which context was manipulated as a within-subjects variable, the only significant source of variance was pattern context: All listeners were better at detecting time changes in regular than in irregular patterns. The results are considered in light of several hypotheses, including the expectancy/contrast model (Jones & Boltz, 1989).

Harmonic, melodic, and frequency height influences in the perception of multivoiced music.

Two experiments addressed the influences of harmonic relations, melody location, and relative frequency height on the perceptual organization of multivoiced music. In Experiment 1, listeners detected pitch changes in multivoiced piano music. Harmonically related pitch changes and those in the middle-frequency range were least noticeable. All pitch changes were noticeable in the high-frequency voice containing the melody (the most important voice), suggesting that melody can dominate harmonic relations. However, the presence of upper partials in the piano timbre used may have accounted for the harmonic effects. Experiment 2 employed pure sine tones, and replicated the effects of Experiment 1. In addition, the influence of the high-frequency melody on the noticeability of harmonically related pitches was lessened by the presence of a second melody. These findings suggest that harmonic, melodic, and relative frequency height relationships among voices interact in the perceptual organization of multivoiced music.

Effects of increasing dietary polyunsaturated fatty acids within the guidelines of the AHA step 1 diet on plasma lipid and lipoprotein levels in normal males.

We attempted to ascertain the effects of polyunsaturated fatty acids by conducting two studies in normal young men, in which monounsaturated fats were replaced by polyunsaturated fats within the guidelines of the American Heart Association step 1 diet. Study A employed a randomized parallel design in which subjects first consumed an average American diet (AAD) containing 37% of calories as fat (saturated fat, 16% calories; monounsaturated fat, 14% calories; and polyunsaturated fat, 7% calories). After 3 weeks, one third of the subjects continued with the AAD, one third switched to a step 1 diet in which total fat calories were reduced to 30% by replacing saturated fat with carbohydrate, and one third switched to a polyunsaturated fat-enriched (Poly) diet with the same 30% fat calories and a reduction of monounsaturated fat from 14% to 8% and an increase of polyunsaturated fat from 7% to 13% of calories. The randomized period lasted 6 weeks. Total and low-density lipoprotein (LDL) cholesterol levels on the step 1 and Poly diets were reduced compared with levels on the AAD (P < .001). Total and LDL cholesterol did not differ between the step 1 and Poly diets, although comparison between the two diets is limited by the small study groups. Serum apolipoprotein (apo) B levels fell on the Poly diet compared with the AAD. Total high-density lipoprotein (HDL), HDL2, and HDL3 cholesterol levels were not significantly affected by the diets. Postprandial lipid and lipoprotein concentrations did not significantly differ either. In study B, a randomized crossover design was used in which all subjects ate the step 1 and Poly diets for 5 weeks each with a 4-day break between diets. In the eight subjects studied, the values for fasting plasma total, LDL, and HDL cholesterol; triglycerides; apoB; and apoA-I were essentially identical at the end of each diet period. Postprandial triglyceride areas obtained after ingestion of a large, standard fat load were also the same. Finally, LDL apoB and HDL apoA-I turnovers were unaffected by replacement of monounsaturates with polyunsaturates. In summary our results indicate that modest exchanges of monounsaturated for polyunsaturated fats do not significantly affect LDL or HDL levels or metabolism, which supports the view that reducing saturated fats is the key to lowering total and LDL cholesterol.

A dose-response study of the effects of dietary cholesterol on fasting and postprandial lipid and lipoprotein metabolism in healthy young men.

Despite many previous studies, controversy remains concerning the effects of dietary cholesterol on plasma cholesterol concentrations. In addition, the focus of previous studies has been fasting lipid and lipoprotein concentrations; there are no published studies with postprandial measurements. We studied the effects of four levels of dietary cholesterol intake on fasting lipid, lipoprotein, and apoprotein levels, as well as postprandial lipid levels, in a group of young, healthy men who were otherwise eating a low-fat, American Heart Association step 1 diet. Twenty young, healthy men completed a randomized, four-way crossover design study to test the effects of an American Heart Association step 1 diet containing 0, 1, 2, or 4 eggs per day. Dietary cholesterol ranged from 128 to 858 mg cholesterol per day. Each diet was eaten for 8 weeks, with a break between diets. Three fasting blood samples were obtained at the end of each diet period. In addition, blood samples were obtained just before and 2, 4, and 6 hours after ingestion of a standard lunch containing the various amounts of egg cholesterol. We also obtained blood 4 and 8 hours after the subjects ingested a standard, high-fat formula. Fasting plasma total cholesterol concentrations increased by 1.47 mg/dL (0.038 mmol/L) for every 100 mg dietary cholesterol added to the diet (P < .001). Low-density lipoprotein (LDL) cholesterol increased in parallel. Responsiveness varied but appeared to be normally distributed. Fasting plasma apoprotein B concentrations increased approximately 10% between the 0- and 4-egg diets and were correlated with changes in total and LDL cholesterol concentrations. Although there was a trend toward a greater response in men with an apoprotein E4 allele, this was not statistically significant. Fasting plasma cholesteryl ester transfer protein levels were higher only on the 4-egg diet, and changes in cholesteryl ester transfer protein levels between the 0- and 4-egg diets correlated with changes in total and LDL cholesterol. There were no differences in the postlunch or post-fat-formula responses of plasma lipids across the diets. Incubation of the 4-hour postlunch serum with J774 macrophages did not affect cell cholesteryl ester content at any level of dietary cholesterol. Cellular free cholesterol levels were slightly higher on each of the egg-containing diets versus the 0-egg diet. In summary, increases in dietary cholesterol resulted in linear increases in fasting total and LDL cholesterol in young, healthy men.(ABSTRACT TRUNCATED AT 400 WORDS)

Reducing total dietary fat without reducing saturated fatty acids does not significantly lower total plasma cholesterol concentrations in normal males.

Forty-eight healthy male students ate an average American diet (AAD) with 37% of calories from fat and 16% from saturated fatty acids for 3 wk. During the next 7 wk, one-third of the students continued to eat the AAD, one-third switched to a 30%-fat diet with 9% saturated fatty acids (Step 1 diet), and one-third switched to a 30%-fat diet with 14% saturated fatty acids (Sat diet). The Step 1 group had a significant reduction in plasma total cholesterol (TC) (0.36 +/- 0.37 mmol/L) compared with the AAD group (0.07 +/- 0.39 mmol/L) and the Sat group (0.08 +/- 0.25 mmol/L). The Sat group did not differ from the AAD group. Changes in low-density-lipoprotein (LDL) cholesterol paralleled changes in total cholesterol. High-density-lipoprotein cholesterol fell significantly in the Step 1 group (0.11 +/- 0.08 mmol/L) compared with the AAD group. Plasma triglycerides did not differ between groups at the end of the randomized periods. In summary, reduction of dietary fat intake from 37% to 30% of calories did not lower plasma total and LDL cholesterol concentrations unless the reduction in total fat was achieved by decreasing saturated fatty acids.

The will and the ways: development and validation of an individual-differences measure of hope.

Defining hope as a cognitive set that is composed of a reciprocally derived sense of successful (a) agency (goal-directed determination) and (b) pathways (planning of ways to meet goals), an individual-differences measure is developed. Studies demonstrate acceptable internal consistency and test-retest reliability, and the factor structure identifies the agency and pathways components of the Hope Scale. Convergent and discriminant validity are documented, along with evidence suggesting that Hope Scale scores augmented the prediction of goal-related activities and coping strategies beyond other self-report measures. Construct validational support is provided in regard to predicted goal-setting behaviors; moreover, the hypothesized goal appraisal processes that accompany the various levels of hope are corroborated.

Lack of effect of lovastatin therapy on the parameters of whole-body cholesterol metabolism.

UNLABELLED: The effects of lovastatin therapy on the parameters of body cholesterol metabolism were explored in nine hypercholesterolemic patients. Long-term cholesterol turnover studies were performed before therapy, and were repeated after 15 mo of lovastatin therapy (40 mg/d) while continuing on therapy. The major question addressed was whether a reduction in plasma cholesterol level with lovastatin would be associated with a reduction in the whole-body production rate of cholesterol or with the sizes of exchangeable body cholesterol pools as determined by the three-pool model of cholesterol turnover. The mean plasma cholesterol level decreased 19.4% (from 294 to 237 mg/dl), and low-density lipoprotein cholesterol decreased 23.8% (from 210 to 159 mg/dl) with lovastatin therapy. Changes in high-density lipoprotein cholesterol level were not significant. The cholesterol production rate did not change significantly with therapy (1.09 +/- 0.10 [mean +/- S.D.] vs. 1.17 +/- 0.09 g/d). By comparison, colestipol and niacin treatment in three other subjects more than doubled the cholesterol production rate (1.14 +/- 0.28 vs. 2.42 +/- 0.34 g/d). Thus, hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibition by lovastatin at the therapeutic dose used here did not change the steady-state rate of whole-body cholesterol synthesis. Despite the changes in plasma cholesterol levels, no significant changes were seen in the values of M1, of M3 or of Mtot, the sizes of the pools of rapidly, of slowly, and of total body exchangeable cholesterol. CONCLUSION: lovastatin therapy to lower plasma cholesterol does not lead to corresponding reductions in body cholesterol pools or to a reduction in the rate of whole-body cholesterol synthesis. In the new steady state that exists during long-term lovastatin therapy, along with increased expression of the genes for HMG-CoA reductase and the LDL receptor, the body compensates for the effects of the drug so that cholesterol production rate and tissue pool sizes are not changed from pretreatment values.

Reduction of plasma cholesterol levels in normal men on an American Heart Association Step 1 diet or a Step 1 diet with added monounsaturated fat.

The design of diets to achieve optimal changes in plasma lipid levels is controversial. In a randomized, double-blind trial involving 36 healthy young men, we evaluated the effects on plasma lipid levels of both an American Heart Association Step 1 diet (in which 30 percent of the total calories were consumed as fat: 10 percent saturated, 10 percent monounsaturated, and 10 percent polyunsaturated fats, with 250 mg of cholesterol per day) and a monounsaturated fat-enriched Step 1 diet (with 38 percent of the calories consumed as fat: 10 percent saturated, 18 percent monounsaturated, and 10 percent polyunsaturated fats, with 250 mg of cholesterol per day). The effects of these diets were then compared with those of an average American diet, in which 38 percent of the total calories were consumed as fat: 18 percent saturated, 10 percent monounsaturated, and 10 percent polyunsaturated fats, with 500 mg of cholesterol per day. The men consumed the average American diet for 10 weeks before random assignment to one of the two Step 1 diets or to continuation of the average diet for an additional 10 weeks. Caloric intake was adjusted to maintain a constant body weight. As compared with the mean (+/- SD) change in the plasma total cholesterol level in the group that followed the average American diet throughout the study (-0.05 +/- 0.36 mmol per liter), there were statistically significant reductions (P less than 0.025) in the plasma total cholesterol level in the group on the Step 1 diet (-0.37 +/- 0.27 mmol per liter) and in the group on the monounsaturated fat-enriched Step 1 diet (-0.46 +/- 0.36 mmol per liter). There were parallel reductions in the plasma low-density lipoprotein cholesterol levels in these two groups. Neither the plasma triglyceride levels nor the high-density lipoprotein cholesterol concentrations changed significantly with any diet. We conclude that enrichment of the Step 1 diet with monounsaturated fat does not alter the beneficial effects of the Step 1 diet on plasma lipid concentrations.